We will determine the extent of the antibody clonotype repertoire directd against hen eggwhite lysozyme by the use of probes that can define specific sub populations of the total array-e.g. binding of lysozyme peptides, or distantly related lysozymes. How many clonotypes are directed against a single epitope? The mechanism underlying clonal dominance will be studied in clonal interaction studies where we have the specificity markers available to trigger each clonal precursor at will and then watch its development. We will explore the modulating effect of anti-idiotype serum in this system. Responses to which epitopes are affected by dominant clones; by suppressive T-cells? We will try to "steer" the specificity of the anti-lysozyme response via the T-cell, first by peptide priming and second by forcing tolerant mice to respond to very closely related lysozymes. Primed T-cell specificity will be studied by inhibition of helper function with defined peptides. The development and propagation of T and B-cell clones will be followed to study the persistance of certain clones, their replacement by others, and possible exhaustion of memory to defined specificities. It may be possible to determine to what extent specificity of expression reflects specificity for antigen in the immunized animal. BIBLIOGRAPHIC REFERENCES: Hill, S., R.L. Yowell, D.E. Kipp, R.J. Scobienski, A. Miller and E. Sercarz. Overcoming Ir gene control of the response to the lysozymes. Advances in Experimental Medicine and Biology (in press, 1976). Kipp, D.E., E.E. Sercarz and A. Miller. Multigenic, H-2 linked control of the mouse immune response to human lysozyme (HUL). (abstract, FASEB 1976).